Is minimal-accessed (endoscopic- or robotic-assisted) nipple-sparing mastectomy contraindicated for large breasts?

BACKGROUND: In the developmental stage of minimal-accessed nipple-sparing mastectomy (MA-NSM), selecting patients with small to medium-sized breasts was common for better cosmetic outcomes and oncological safety. However, the suitability of MA-NSM for large, ptotic breasts remained uncertain. This retrospective study aim to assess MA-NSM outcomes in patients with large breasts. MATERIALS AND METHODS: This retrospective study included patients receiving conventional NSM (C-NSM) and MA-NSM from January 2011 to September 2022, at a single institution. We analyzed perioperative parameters and clinical outcomes based on breast specimen size, classified as small (≤300 g), medium (>300-450 g), large (>450-600 g), and very large (>600 g). RESULTS: A total of 728 patients was enrolled. C-NSM was performed in 51% (371/728) of cases, while MA-NSM was done in 49% (357/728). The overall complication rate of MA-NSM was comparable to C-NSM (p = 0.573), but severe complications (Clavien-Dindo, CD III) was significantly reported more following C-NSM, regardless of breast size. During a median follow-up of 52 months, no significant difference in oncological outcomes was observed. Comparing MA-NSM and C-NSM outcomes in large-very large breasts (>450 g), MA-NSM demonstrated significantly less blood loss (p = 0.036) and lower incidence of severe complications (CD ≥ III) compared to C-NSM (p = 0.002). CONCLUSION: MA-NSM is feasible for large breasts and offers benefits by reducing blood loss and decreasing the incidence of severe complications (CD ≥ III) in this patient group.

Scarless totally implantable venous access port (TIVAP) implantation: Surgical technique, preliminary results, learning curve, and patients-reported outcome in 125 breast cancer patients.

BACKGROUND: Minimal-access (endoscopic or robotic-assisted) breast surgery has been increasingly performed and shown better cosmetic results. However, location of totally implantable venous access port (TIVAP) for systemic treatment at anterior chest may compromise its aesthetic benefits. Therefore, we proposed a new scarless technique for TIVAP implantation, and reported the preliminary results, learning curve, and patients-surveyed outcome. METHODS: Surgical technique of the new "scarless" TIVAP implantation was proposed. Patients receiving this procedure in a single institution were included. The preliminary results of the scarless TIVAP implantation, learning curve, and patient-reported outcome were analyzed and reported. RESULTS: A total of 125 breast cancer patients received scarless TIVAP procedures were enrolled. The primary success rate of the scarless TIVAP implantation was 100%. Mean operative time was 46 ± 14 min. Mean amount of blood loss was 8.5 ± 3.2 ml. The cumulative sum plot showed operation time significantly decreased after 24th cases. In the initial learning phase, the mean operative time was 55 ± 17 min, and decreased to 43 ± 12 min in the later mature phase (P = 0.003). There were 5 (4%) complications detected, which included 1 (0.8%) seroma formation, 2 (1.6%) revisions, and 2 (1.6%) unplanned explantations. From patients-evaluated questionnaires, more than 90% of responders were satisfied with aesthetic results, experience during surgery, and application of scarless TIVAP for systemic therapy. CONCLUSIONS: The scarless TIVAP implantation is a safe & reliable procedure with high patients-reported aesthetic satisfaction, and could be an alternative TIVAP procedure for patients requiring chemotherapy and desiring a less noticeable scar.

Reliability of predicting low-burden (≤ 2) positive axillary lymph nodes indicating sentinel lymph node biopsy in primary operable breast cancer - a retrospective comparative study with PET/CT and breast MRI.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in early breast cancer patients with low-burden axillary metastasis (≤ 2 positive nodes). This study aimed to determine the diagnostic performances of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and breast magnetic resonance imaging in detecting axillary lymph node (ALN) metastases and the reliability to predict ALN burden. METHODS: A total of 275 patients with primary operable breast cancer receiving preoperative PET/CT and upfront surgery from January 2001 to December 2022 in a single institution were enrolled. A total of 244 (88.7%) of them also received breast MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT and breast MRI were assessed. The predictive values to determine ALN burden were evaluated using radio-histopathological concordance. RESULTS: PET/CT demonstrated a sensitivity of 53.4%, specificity of 82.1%, PPV of 65.5%, NPV of 73.5%, and accuracy of 70.9% for detecting ALN metastasis, and the corresponding values for MRI were 71.8%, 67.8%, 56%, 80.8%, and 69.2%, respectively. Combining PET/CT and MRI showed a significantly higher PPV than MRI (72.7% vs 56% for MRI alone, p = 0.037) and a significantly higher NPV than PET/CT (84% vs 73.5% for PET/CT alone, p = 0.041). For predicting low-burden axillary metastasis (1-2 positive nodes), the PPVs were 35.9% for PET/CT, 36.7% for MRI, and 55% for combined PET/CT and MRI. Regarding patients with 0-2 positive ALNs in imaging, who were indicated for SLNB, the predictive correctness was 96.1% for combined PET/CT and MRI, 95.7% for MRI alone, and 88.6% for PET/CT alone. CONCLUSIONS: PET/CT and breast MRI exhibit high predictive values for identifying low-burden axillary metastasis in patients with operable breast cancer with ≦ 2 positive ALNs on imaging.

Robotic Versus Conventional or Endoscopic-assisted Nipple-sparing Mastectomy and Immediate Prosthesis Breast Reconstruction in the Management of Breast Cancer: A Prospectively Designed Multicenter Trial Comparing Clinical Outcomes, Medical Cost, and Patient-reported Outcomes (RCENSM-P).

OBJECTIVE: To compare the clinical and patient-reported outcomes of minimal access and conventional nipple-sparing mastectomy (C-NSM). The secondary outcomes investigated included medical costs and oncological safety. BACKGROUND: Minimal-access NSM has been increasingly applied in the treatment of patients with breast cancer. However, prospective multicenter trials comparing robotic-assisted NSM (R-NSM) versus C-NSM or endoscopic-assisted NSM (E-NSM) are lacking. METHODS: A prospectively designed 3-arm multicenter, nonrandomized trial (NCT04037852) was conducted from October 1, 2019 to December 31, 2021, to compare R-NSM with C-NSM or E-NSM. RESULTS: A total of 73 R-NSM, 74 C-NSM, and 84 E-NSM procedures were enrolled. The median wound length and operation time of C-NSM was (9 cm, 175 minutes), (4 cm, and 195 minutes) in R-NSM, and (4 cm and 222 minutes) in E-NSM. Complications were comparable among the groups. Better wound healing was observed in the minimal-access NSM group. The R-NSM procedure was 4000 and 2600 United States Dollars more expensive than C-NSM and E-NSM, respectively. Wound/scar and postoperative acute pain evaluation favored the use of minimal access NSM over C-NSM. Quality of life in terms of chronic breast/chest pain, mobility, and range of motion of the upper extremity showed no significant differences. The preliminary oncologic results showed no differences among the 3 groups. CONCLUSIONS: R-NSM or E-NSM is a safe alternative if compared with C-NSM in terms of perioperative morbidities, especially with better wound healing. The advantage of minimal access groups was higher wound-related satisfaction. Higher costs remain one of the major limiting factors in the widespread adoption of R-NSM.

Single-port three-dimensional (3D) endoscopic-assisted breast surgery-preliminary results and patient-reported satisfaction in 145 breast cancer and gynecomastia cases.

BACKGROUND: Minimal-accessed (robotic and endoscopic) breast cancer surgery is increasingly performed due to better cosmetic results and acceptable oncological outcomes. This study aims to demonstrate the clinical safety and patient-reported cosmetic satisfaction of single-port three-dimensional endoscopic-assisted breast surgery (S-P 3D EABS), which is our new endoscopic surgical innovation, in both malignant and benign breast conditions. METHODS: Patients who underwent S-P 3D EABS from 1 August 2018 to 31 July 2022 in a single institution were enrolled. Clinical outcomes of this procedure were retrospectively reviewed, and the patient-reported cosmetic satisfaction was evaluated by a questionnaire and reported herein. RESULTS: During the study period, 145 patients underwent 164 procedures of S-P 3D EABS. One hundred fifty (91.5%) procedures were endoscopic-assisted nipple-sparing mastectomy (S-P 3D E-NSM; 117 therapeutic procedures for breast cancer, 13 prophylactic mastectomies, 20 procedures for gynecomastia). Fourteen (8.5%) procedures of endoscopic-assisted breast-conserving surgery (S-P 3D E-BCS) were performed (12 S-P 3D E-BCS, 2 S-P 3D E-BCS with 3D videoscope-assisted partial breast reconstruction, which was 1 case of latissimus dorsi flap and 1 case of omental flap). The mean operative time was 245 ± 110 min in S-P 3D E-NSM and 260 ± 142 min in S-P 3D E-BCS. The mean intraoperative blood loss was 49.7 ± 46.9 ml in S-P 3D E-NSM and 32.8 ± 17.5 ml in S-P 3D E-BCS. Subnipple biopsy showed positive malignancy in 3 (2.6%) S-P 3D E-NSM patients. None of the S-P 3D E-BCS patients found margin involvement; however, 3 (2.6%) reported margin involvement in S-P 3D E-NSM patients. Thirty-two complications were found (24.6%): 7 (5.3%) transient nipple-areolar complex (NAC) ischemia, 7 (5.3%) partial NAC necrosis, 1 (0.7%) total NAC necrosis, and 1 (0.7%) implant loss. During the mean follow-up time of 34 months, there were 2 (1.5%) patients with locoregional recurrence, 9 (6.9%) distant metastasis, and 2 (1.5%) mortality. 78.6% (77/98) of patients answering the cosmetic-evaluated questionnaire reported good and excellent overall satisfaction. CONCLUSIONS: S-P 3D EABS is a novel surgical innovation, which is able to perform safely in either malignant or benign breast conditions and offer promising cosmetic results.

Clinical study on single-port endoscopic resection via a gasless transaxillary approach in the treatment of breast fibroadenoma in adolescents.

BACKGROUND: Breast fibroadenoma is the most common benign breast tumour. This study aimed to investigate the advantages and disadvantages of endoscopic-assisted resection via a gas-less transaxillary single-port approach for breast fibroadenoma in adolescent patients, compared with a traditional approach. METHODS: The clinical data of 83 patients with breast fibroadenoma treated in our hospital from October 2019 to October 2021 were collected for retrospective analysis. These patients were divided into an endoscopic-assisted surgery (ES) group (n = 39) and a traditional open surgery (OS) group (n = 44) according to the surgical approach. The operative time, intraoperative blood loss, incision length, postoperative complications, and patient satisfaction were compared between the two groups. RESULTS: The surgical cost was (5.1 ± 0.6) thousand Yuan [(0.7 ± 0.1) thousand US dollars] in the ES group and (3.5 ± 2.7) thousand Yuan [(0.5 ± 0.4) thousand US dollars] in the OS group, showing a statistically significant difference (p < 0.001). There was no significant difference in surgical time, intraoperative blood loss, incision length, or the rate of postoperative complications between the two groups. Stratified analysis revealed that the ES group had a significantly shorter operative time [(57.00 ± 10.26) min vs. (78.27 ± 7.63)] (p < 0.001), a smaller incision length [(3.73 ± 0.34) cm vs. (4.42 ± 0.44) cm] (p < 0.001), and a lower complication incidence rate (11.1% vs. 63.6) (p = 0.011) than the OS group in the cases with a nodule number ≥ 3. The satisfaction score using the BREAST-Q scale indicated that psychosocial well-being and patient satisfaction with the breast in the ES group were significantly superior to those in the OS group [(91.18 ± 3.12) points vs. (87.00 ± 4.45) points and (91.03 ± 6.80) points vs. (84.45 ± 6.06) points, respectively] (p < 0.001). CONCLUSION: ES is a safe and effective method for the treatment of fibroadenoma. In patients with multiple fibroadenomas (≥ 3 tumours), ES has a shorter operative time and fewer postoperative complications. ES demonstrates a significant, prominent advantage in cosmetic appearance. However, it should be noted that ES is associated with higher costs than OS.

Use of Magnetic Resonance Imaging for Evaluating Residual Breast Tissue After Robotic-Assisted Nipple-Sparing Mastectomy in Women With Early Breast Cancer.

OBJECTIVE: Prospective studies on postoperative residual breast tissue (RBT) after robotic-assisted nipple-sparing mastectomy (R-NSM) for breast cancer are limited. RBT presents an unknown risk of local recurrence or the development of new cancer after curative or risk-reducing mastectomies. This study investigated the technical feasibility of using magnetic resonance imaging (MRI) to evaluate RBT after R-NSM in women with breast cancer. MATERIALS AND METHODS: In this prospective pilot study, 105 patients, who underwent R-NSM for breast cancer at Changhua Christian Hospital between March 2017 and May 2022, were subjected to postoperative breast MRI to evaluate the presence and location of RBT. The postoperative MRI scans of 43 patients (age, 47.8 ± 8.5 years), with existing preoperative MRI scans, were evaluated for the presence and location of RBT. In total, 54 R-NSM procedures were performed. In parallel, we reviewed the literature on RBT after nipple-sparing mastectomy, considering its prevalence. RESULTS: RBT was detected in 7 (13.0%) of the 54 mastectomies (6 of the 48 therapeutic mastectomies and 1 of the 6 prophylactic mastectomies). The most common location for RBT was behind the nipple-areolar complex (5 of 7 [71.4%]). Another RBT was found in the upper inner quadrant (2 of 7 [28.6%]). Among the six patients who underwent RBT after therapeutic mastectomies, one patient developed a local recurrence of the skin flap. The other five patients with RBT after therapeutic mastectomies remained disease-free. CONCLUSION: R-NSM, a surgical innovation, does not seem to increase the prevalence of RBT, and breast MRI showed feasibility as a noninvasive imaging tool for evaluating the presence and location of RBT.

Diagnostic accuracy of pre-operative breast magnetic resonance imaging (MRI) in predicting axillary lymph node metastasis: variations in intrinsic subtypes, and strategy to improve negative predictive value-an analysis of 2473 invasive breast cancer patients.

BACKGROUND: The value and utility of axillary lymph node (ALN) evaluation with MRI in breast cancer were not clear for various intrinsic subtypes. The aim of the current study is to test the potential of combining breast MRI and clinicopathologic factors to identify low-risk groups of ALN metastasis and improve diagnostic performance. MATERIAL AND METHODS: Patients with primary operable invasive breast cancer with pre-operative breast MRI and post-operative pathologic reports were retrospectively collected from January 2009 to December 2021 in a single institute. The concordance of MRI and pathology of ALN status were determined, and also analyzed in different intrinsic subtypes. A stepwise strategy was designed to improve MRI-negative predictive value (NPV) on ALN metastasis. RESULTS: 2473 patients were enrolled. The diagnostic performance of MRI in detecting metastatic ALN was significantly different between intrinsic subtypes (p = 0.007). Multivariate analysis identified tumor size and histologic type as independent predictive factors of ALN metastases. Patients with HER-2 (MRI tumor size ≤ 2 cm), or TNBC (MRI tumor size ≤ 2 cm) were found to have MRI-ALN-NPV higher than 90%, and these false cases were limited to low axillary tumor burden. CONCLUSION: The diagnostic performance of MRI to predict ALN metastasis varied according to the intrinsic subtype. Combined pre-operative clinicopathologic factors and intrinsic subtypes may increase ALN MRI NPV, and further identify some groups of patients with low risks of ALN metastasis, high NPV, and low burdens of axillary disease even in false-negative cases.

Factors associated with alteration of nipple or skin sensation and impact of duration of time following nipple-sparing mastectomy (NSM): an analysis of 460 cases with comparison of conventional versus endoscopic- or robotic-assisted NSM.

BACKGROUND: The current study aims to evaluate the nipple and skin sensation following nipple-sparing mastectomy (NSM) and identify patient-, surgical-, or treatment-related factors affecting nipple or skin sensation in this cohort. METHODS: Patients who received NSM with postoperative nipple and skin sensation test evaluation at a single institution over the past 10 years were retrospectively retrieved from a prospectively collected breast cancer surgery database. RESULTS: A total of 460 NSM procedures were included in this current study, with the mean age of 48.3 ± 9.1. Three-hundred eighty-three (83.3%) patients had breast reconstructions. One-hundred seventy-four (37.8%) received conventional NSM (C-NSM), 195 (42.4%) endoscopic-assisted NSM (E-NSM), and 91 (19.8%) robotic-assisted NSM (R-NSM) procedures. For nipple sensation assessment, 15 (3.3%) were grade 0, 83 (18.2%) grade I, 229 (49.7%) grade II, and 133 (28.9%) grade III (normal sensation), respectively, with mean grade score of 2.1 ± 0.7. The preserved (grade III) nipple sensation rate was 36.2% (63/174) in the C-NSM group, 26.7% (52/195) in the E-NSM group, and 19.7% (18/91) in the R-NSM group (P = 0.06). The "time since surgery to last evaluation" was significantly longer in the C-NSM group (45.6 ± 34 months) or E-NSM group (44.7 ± 35.8 months) as compared to R-NSM group (31.8 ± 16 months, P < 0.01). In multivariate analysis, peri-areolar incision showed higher grade of nipple sensation (OR: 2.1, P = 0.02) compared to upper outer quadrant incision, and longer follow-up time post-NSM showed significant improvement of nipple or skin sensation (> 60 months vs. ≦ 12 months: nipple odds ratio (OR) = 5.75, P < 0.01; skin, OR = 1.97, P < 0.05). CONCLUSION: Our current analysis showed some factors to be related to postoperative nipple or skin sensation, and longer "time after surgery" was associated with significant improvement of nipple and skin sensation in patients who received NSM, regardless of the surgical approaches. SYNOPSIS: Our current analysis showed a significant portion of patients with decrease or loss of nipple or skin sensation after nipple-sparing mastectomy (NSM). Several factors associated with preserved nipple or skin sensation were identified, including age, surgical methods, surgical wound location, and association of time from surgery showing that improvement of partial nipple or skin sensation was evident after a longer follow-up.

Oncoplastic and reconstructive breast surgeon performance and impact on breast reconstructions: Clinical outcomes, learning curve, and patients' satisfaction.

BACKGROUND: Compared to mastectomy alone, the addition of breast reconstruction could improve quality of life and it is usually performed by two-team approach, which consisted of both breast surgeons and plastic surgeons. This study aims to illustrate the positive impacts of the dual-trained oncoplastic reconstructive breast surgeon (ORBS) and reveal the factors influencing reconstruction rates. METHODS: This retrospective study enrolled 542 breast cancer patients who undergone mastectomy with reconstruction performed by a particular ORBS between January 2011 and December 2021 at a single institution. Clinical and oncological outcomes, impact of case accumulation on performance and patient-reported aesthetic satisfactions were analyzed and reported. Furthermore, in this study 1851 breast cancer patients treated with mastectomy combined with or without breast reconstructions, which included 542 performed by ORBS, were reviewed to identify factors affecting breast reconstructions. RESULTS: Among the 524 breast reconstructions performed by the ORBS, 73.6% were gel implant reconstructions, 2.7% were tissue expanders, 19.5% were transverse rectus abdominal myocutaneous (TRAM) flaps, 2.7% were latissimus dorsi (LD) flaps, 0.8% were omentum flaps, and 0.8% involved LD flaps and implants. There was no total flap loss in the 124 autologous reconstructions, and the implant loss rate was 1.2% (5/403). Patient-reported aesthetic evaluations showed that 95% of the patients were satisfied. As the ORBS's accumulated case experiences, the implant loss rate decreased, and the overall satisfaction rate increased. According to the cumulative sum plot learning curve analysis, it took 58 procedures for the ORBS to shorten the operative time. In multivariate analysis, younger age, MRI, nipple sparing mastectomy, ORBS, and high-volume surgeon were factors related to breast reconstruction. CONCLUSION: The current study demonstrated that a breast surgeon after adequate training could become an ORBS and perform mastectomies with various types of breast reconstruction with acceptable clinical and oncological outcomes for breast cancer patients. ORBSs could increase breast reconstruction rates, which remain low worldwide.

Mammographic Density Reduction is Associated to the Prognosis in Asian Breast Cancer Patients Receiving Hormone Therapy.

INTRODUCTION: Using mammographic density as a significant biomarker for predicting prognosis in adjuvant hormone therapy patients is controversial due to the conflicting results of recent studies. This study aimed to evaluate hormone therapy-induced mammographic density reduction and its association with prognosis in Taiwanese patients. METHODS: In this retrospective study, 1941 patients with breast cancer were screened, and 399 patients with estrogen receptor-positive breast cancer who received adjuvant hormone therapy were enrolled. The mammographic density was measured using a fully automatic estimation procedure based on full-field digital mammography. The prognosis included relapse and metastasis during treatment follow-up. The Kaplan-Meier method and Cox proportional hazards model were used for disease-free survival analysis. RESULTS: A mammographic density reduction rate >20.8%, measured preoperatively and after receiving hormone therapy from 12-18 months, was a significant threshold for predicting prognosis in patients with breast cancer. The disease-free survival rate was significantly higher in patients whose mammographic density reduction rate was >20.8% (P = .048). CONCLUSION: This study's findings could help estimate the prognosis for patients with breast cancer and may improve the quality of adjuvant hormone therapy after enlarging the study cohort in the future.

Nipple-areolar complex (NAC) or skin flap ischemia necrosis post nipple-sparing mastectomy (NSM)-analysis of clinicopathologic factors and breast magnetic resonance imaging (MRI) features.

BACKGROUND: The purpose of this study is to identify clinicopathologic factors and/or preoperative MRI vascular patterns in the prediction of ischemia necrosis of the nipple-areola complex (NAC) or skin flap post nipple-sparing mastectomy (NSM). METHODS: We performed a retrospective analysis of 441 NSM procedures from January 2011 to September 2021 from the breast cancer database at our institution. The ischemia necrosis of NAC or skin flap was evaluated in correlation with clinicopathologic factors and types of skin incision. Patients who received NSM with preoperative MRI evaluation were further evaluated for the relationship between vascular pattern and the impact on ischemia necrosis of NAC or skin flap. RESULTS: A total of 441 cases with NSM were enrolled in the current study, and the mean age of the cases was 49.1 ± 9.8 years old. A total of 41 (9.3%) NSM procedures were found to have NAC ischemia/necrosis. Risk factors were evaluated of which old age, large mastectomy specimen weight (> 450 g), and peri-areola incision were identified as predictors of NAC necrosis. Two-hundred seventy NSM procedures also received preoperative MRI, and the blood supply pattern was 18% single-vessel type and 82% double-vessel pattern. There were no correlations between MRI blood supply patterns or types of skin flap incisions with ischemia necrosis of NAC. There were also no correlations between blood loss and the pattern or size of the blood vessel. CONCLUSION: Factors such as the type of skin incision, age, and size of mastectomy weight played an important role in determining ischemia necrosis of NAC; however, MRI vascular (single or dual vessel supply) pattern was not a significant predictive factor.

USP7 Induces Chemoresistance in Triple-Negative Breast Cancer via Deubiquitination and Stabilization of ABCB1.

Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer. TNBC does not express the estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. Cytotoxic chemotherapy and surgery are the current therapeutic strategies for TNBC patients, but the chemoresistance of TNBC limits the efficiency of this strategy and shortens the lifespan of patients. The exploration of targeted therapy is ongoing in TNBC research. The aim of the present study was to identify the mechanism underlying acquired resistance in TNBC through the exploration of the relationship between the expression of USP7 and of ABCB1. We found that ubiquitin specific protease 7 (USP7) is a potential therapeutic target for overcoming the chemoresistance of TNBC. USP7 overexpression increased the chemoresistance of TNBC, while the knockdown of USP7 effectively increased the chemosensitivity of chemoresistant TNBC. A USP7 inhibitor effectively induced apoptosis and suppressed metastasis in chemoresistant TNBC. We further clarified that USP7 is a specific deubiquitinating enzyme for ABCB1 that plays an essential role in drug resistance. USP7 directly interacted with ABCB1 and regulated its stability. We concluded that USP7 promotes the chemoresistance of TNBC by stabilizing the ABCB1 protein.

Semantic Segmentation of the Malignant Breast Imaging Reporting and Data System Lexicon on Breast Ultrasound Images by Using DeepLab v3.

In this study, an advanced semantic segmentation method and deep convolutional neural network was applied to identify the Breast Imaging Reporting and Data System (BI-RADS) lexicon for breast ultrasound images, thereby facilitating image interpretation and diagnosis by providing radiologists an objective second opinion. A total of 684 images (380 benign and 308 malignant tumours) from 343 patients (190 benign and 153 malignant breast tumour patients) were analysed in this study. Six malignancy-related standardised BI-RADS features were selected after analysis. The DeepLab v3+ architecture and four decode networks were used, and their semantic segmentation performance was evaluated and compared. Subsequently, DeepLab v3+ with the ResNet-50 decoder showed the best performance in semantic segmentation, with a mean accuracy and mean intersection over union (IU) of 44.04% and 34.92%, respectively. The weighted IU was 84.36%. For the diagnostic performance, the area under the curve was 83.32%. This study aimed to automate identification of the malignant BI-RADS lexicon on breast ultrasound images to facilitate diagnosis and improve its quality. The evaluation showed that DeepLab v3+ with the ResNet-50 decoder was suitable for solving this problem, offering a better balance of performance and computational resource usage than a fully connected network and other decoders.

Profiling of Protein Adducts of Estrogen Quinones in 5-Year Survivors of Breast Cancer Without Recurrence.

AIMS: The aim of this study was to simultaneously analyze estrogen quinone-derived adducts, including 17ß-estradiol-2,3-quinone (E2-2,3-Q) and 17ß-estradiol-3,4-quinone (E2-3,4-Q), in human albumin (Alb) and hemoglobin (Hb) derived from breast cancer patients with five-year postoperative treatment without recurrence in Taiwan and to evaluate the treatment-related effects on the production of these adducts. SETTINGS AND DESIGN: CohortMethods and Material: Blood samples derived from breast cancer 5-year survivors without recurrence were collected. Albumin and hemoglobin adducts of E2-3,4-Q and E2-2,3-Q were analyzed to evaluate the degree of disposition of estrogen to quinones and to compare these adduct levels with those in patients before treatment. STATISTICAL ANALYSIS: All data are expressed as mean ± standard deviation of three determinations. We used Student's t-test to examine subgroups. Data were transformed to the natural logarithm and tested for normal distribution for parametric analyses. Linear correlations were investigated between individual adduct levels by simple regression. Statistical analysis was performed using the SPSS Statistics 20.0. RESULTS: Result confirmed that logged levels of E2-2,3-Q-derived adducts correlated significantly with those of E2-3,4-Q-derived adducts (correlation coefficient r=.336-.624). Mean levels of E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb in 5-year survivors were reduced by 60-70% when compared to those in the breast cancer patients with less than one year of diagnosis/preoperative treatment (P<.001). CONCLUSIONS: Our findings add support to the theme that hormonal therapy including aromatase inhibitors and Tamoxifen may dramatically reduce burden of estrogen quinones. We hypothesize that combination of treatment-related effects and environmental factors may modulate estrogen homeostasis and diminish the production of estrogen quinones in breast cancer patients.

The impact of body mass index (BMI) on MRI diagnostic performance and surgical management for axillary lymph node in breast cancer.

BACKGROUND: We hypothesized that different BMI might have different impact on pre-operative MRI axillary lymph node (ALN) prediction accuracy and thereby subsequent surgical lymph node management. The aim of this study is to evaluate the effect of BMI on presentation, surgical treatment, and MRI performance characteristics of breast cancer with the main focus on ALN metastasis evaluation. METHODS: The medical records of patients with primary invasive breast cancer who had pre-operative breast MRI and underwent surgical resection were retrospectively reviewed. They were categorized into 3 groups in this study: underweight (BMI < 18.5), normal (BMI of 18.5 to 24), and overweight (BMI > 24). Patients' characteristics, surgical management, and MRI performance for axillary evaluation between the 3 groups were compared. RESULTS: A total of 2084 invasive breast cancer patients with a mean age of 53.4 ± 11.2 years were included. Overweight women had a higher rate of breast conserving surgery (56.7% vs. 54.5% and 52.1%) and initial axillary lymph node dissection (15.9% vs. 12.2% and 8.5%) if compared to normal and underweight women. Although the post-operative ALN positive rates were similar between the 3 groups, overweight women were significantly found to have more axillary metastasis on MRI compared with normal and underweight women (50.2% vs 37.7% and 18.3%). There was lower accuracy in terms of MRI prediction in overweight women (65.1%) than in normal and underweight women (67.8% and 76.1%). CONCLUSION: Our findings suggest that BMI may influence the diagnostic performance on MRI on ALN involvement and the surgical management of the axilla in overweight to obese women with breast cancer.

Nafamostat mesylate overcomes endocrine resistance of breast cancer through epigenetic regulation of CDK4 and CDK6 expression.

Breast cancer is common worldwide, and the estrogen receptor-positive subtype accounts for approximately 70% of breast cancer in women. Tamoxifen and fulvestrant are drugs currently used for endocrinal therapy. Breast cancer exhibiting endocrine resistance can undergo metastasis and lead to the death of breast cancer patients. Drug repurposing is an active area of research in clinical medicine. We found that nafamostat mesylate, clinically used for patients with pancreatitis and disseminated intravascular coagulation, acts as an anti-cancer drug for endocrine-resistant estrogen receptor-positive breast cancer (ERPBC). Epigenetic repression of CDK4 and CDK6 by nafamostat mesylate induced apoptosis and suppressed the metastasis of ERPBC through the deacetylation of Histone 3 Lysine 27. A combination of nafamostat mesylate and CDK4/6 inhibitor synergistically overcame endocrine resistance in ERPBC. Nafamostat mesylate might be an essential adjuvant or alternative drug for the treatment of endocrine-resistant ERPBC due to the low cost-efficiency of the CDK4/6 inhibitor.

Minimal Access (Endoscopic and Robotic) Breast Surgery in the Surgical Treatment of Early Breast Cancer-Trend and Clinical Outcome From a Single-Surgeon Experience Over 10 Years.

OBJECTIVE: Endoscopic assisted breast surgery (EABS) or robotic assisted breast surgery (RABS) performed through minimal axillary and/or peri-areolar incisions has become the representative of minimal access breast surgery (MABS). We report the trend and clinical outcome of MABS for treatment of breast cancer. METHODS: Information on patients who underwent breast cancer operation by the principal investigator during the period of 2011 to 2020 was collected from a single institute for analysis. The clinical outcome, trend, and cost of MABS were analyzed and compared with conventional breast surgery (CBS). RESULTS: A total of 824 breast cancer patients operated by a single surgeon were enrolled in this study: 254 received CBS and 570 received MABS, namely, 476 EABS and 94 RABS. From 2011 to 2020, the number of MABS performed annually has shown an increasing trend. Compared with CBS, MABS such as breast conserving surgery and nipple sparing mastectomy (NSM) have effectively reduced wound scar length. Since the sequential uprise from conventional NSM (C-NSM), dual-axillary-areolar-incision two dimensional (2D) endoscopic assisted NSM (E-NSM), single-axillary-incision E-NSM, robotic assisted NSM (R-NSM), and single-port 3D E-NSM, the development of minimal access mastectomies increasingly paralleled with NSM. The operation time of various MABS decreased significantly and showed no statistical difference compared with CBS. R-NSM was associated with highest cost, followed by 3D E-NSM, E-NSM, and C-NSM. The positive surgical margin rate and local recurrence rate of MABS and CBS were not statistically different. CONCLUSION: MABS showed comparable clinical outcome and preliminary oncologic safety as CBS and has been increasingly performed as the surgical treatment of breast cancer, especially minimal access NSM.

Impact of pre-operative breast magnetic resonance imaging on contralateral synchronous and metachronous breast cancer detection-A case control comparison study with 1468 primary operable breast cancer patients with mean follow-up of 102 months.

BACKGROUND: Women with unilateral breast cancer are at an increased risk for the development of contralateral breast cancers. We hypothesis that combined breast MRI would detect more contralateral synchronous breast cancer than conventional imaging alone, and resulted in less contralateral metachronous breast cancer during follow-up. METHODS: We retrospectively collected two groups of breast cancer patients diagnosed from 2009 to 2013 for evaluating the effectiveness and value of adding pre-operative breast MRI to conventional breast images (mammography and sonography) for detection of contralateral synchronous breast cancer. The new metachronous contralateral breast cancer diagnosed during follow-up was prospectively evaluated and compared. RESULTS: Group A (n = 733) comprised patients who underwent conventional preoperative imaging and group B (n = 735) combined with MRI were enrolled and compared. Seventy (9.5%) of the group B patients were found to have contralateral lesions detected by breast MRI, and 65.7% of these lesions only visible with MRI. The positive predictive value of breast MRI detected contralateral lesions was 48.8%. With the addition of breast MRI to conventional imaging studies, more surgical excisions were performed in contralateral breasts (6% (44/735) versus 1.4% (10/733), P< 0.01), more synchronous contralateral breast cancer detected (2.9% (21/735) versus 1.1% (8/733), P = 0.02), and resulted in numerical less (2.2% (16/714) versus 3% (22/725), p = 0.3) metachronous contralateral breast cancer during a mean follow-up of 102 months. CONCLUSIONS: Our study provides useful estimates of the pre-operative breast MRI for the increased detection of contralateral synchronous breast cancer and less subsequent contralateral metachronous breast cancer.

Ergosta-7,9(11),22-trien-3ß-ol Attenuates Inflammatory Responses via Inhibiting MAPK/AP-1 Induced IL-6/JAK/STAT Pathways and Activating Nrf2/HO-1 Signaling in LPS-Stimulated Macrophage-like Cells.

Chronic inflammation induces autoimmune disorders and chronic diseases. Several natural products activate nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, attenuating inflammatory responses. Ergosta-7,9(11),22-trien-3ß-ol (EK100) isolated from Cordyceps militaris showed anti-inflammatory and antioxidative activity, but those mechanisms are still unclear. This study is the first to investigate EK100 on antioxidant Nrf2 relative genes expression in LPS-stimulated macrophage-like cell lines. The results showed that EK100 reduced IL-6 (interleukin-6) and tumor necrosis factor-α production. EK100 also attenuated a mitogen-activated protein kinase/activator protein-1 (MAPK/AP-1) pathway and interleukin-6/Janus kinase/signal transducer and activator of transcription (IL-6/JAK/STAT) pathway in LPS-stimulated cells. Toll-like receptor 4 (TLR4) inhibitor CLI-095 and MAPK inhibitors can synergize the anti-inflammatory response of EK100 in LPS-stimulated cells. Moreover, EK100 activated Nrf2/HO-1 (heme oxygenase-1) signaling in LPS-stimulated murine macrophage-like RAW 264.7 cells, murine microglial BV2 cells, and human monocytic leukemia THP-1 cells. However, Nrf2 small interfering RNA (Nrf2 siRNA) reversed EK100-induced antioxidative proteins expressions. In conclusion, EK100 showed anti-inflammatory responses via activating the antioxidative Nrf2/HO-1 signaling and inhibiting TLR4 related MAPK/AP-1 induced IL-6/JAK/STAT pathways in the LPS-stimulated cells in vitro. The results suggest EK100 acts as a novel antioxidant with multiple therapeutic targets that can potentially be developed to treat chronic inflammation-related diseases.